Akt1 and Jak1 siRNA based silencing effects on the proliferation and apoptosis in head and neck squamous cell carcinoma.

Based on Akt1 and Jak1 key roles in apoptosis and proliferation of many cancers, the aim of this study was to find a new gene therapy strategy by silencing of these main anti-apoptotic genes for HNSCC treatment. Cancerous HN5 and normal HUVEC cell lines were treated with Akt1 and Jak1 siRNAs alone or with each other combined with/without cisplatin. The MTS, flow cytometry, 4',6-diamidino-2-phenylindole staining, real-time PCR and ELISA methods were utilized in this study. The highest percentage of apoptosis was observed in the treatment of Jak1 siRNA/cisplatin group in cancerous HN5 cells (96.5%) where this treatment showed 12.84% apoptosis in normal HUVEC cell line. Cell viability reduced significantly to 64.57% after treatment with Akt1 siRNA in HN5 treated group. Knocking down Akt1 and Jak1 genes using siRNAs could increase levels of apoptosis and reduce proliferation rate in HNSCC indicating the powerful effects of these genes siRNAs with or without chemotherapeutic agents in HNSCC treatment. In conclusion, the combination of siRNA-mediated gene-silencing strategy can be considered as a valuable and safe approach for sensitizing cancer cells to chemotherapeutic agents thus proposed further studies regarding this issue to approve some siRNA based therapeutics for using in clinic.

The role of macrophages and eosinophils in reactive lesions of the oral cavity.

BACKGROUND: Many studies have reported that macrophages and eosinophils are involved in the pathogenesis of several diseases. To the best of our knowledge, this is the first study comparing macrophages and eosinophils in oral reactive lesions. AIMS: In this study, we aimed to determine the contribution of macrophages and eosinophils to the pathogenesis of oral reactive lesions and the relationships between these biomarkers and the diverse histopathologic features. METHODS: Seventy-five paraffin-embedded tissue samples were assessed in this study. Five categories (15 cases for each group), including peripheral ossifying fibroma, pyogenic granuloma, fibroma, inflammatory fibrous hyperplasia, and peripheral giant-cell granuloma, were considered. Anti-CD68 immunohistochemical and hematoxylin-eosin staining was carried out. RESULTS: We found that macrophages, but not eosinophils, were a significant internal component of oral reactive lesions. Macrophages were observed in high densities in all studied groups and diffusely distributed or clustered throughout these lesions. The number of macrophages was increased in peripheral giant-cell granuloma compared with other groups. CONCLUSIONS: Our findings suggest that macrophages are involved in the pathogenesis and the variation of microscopic features of oral reactive lesions. However, further clinical studies should be conducted to identify the biological process behind macrophages and the molecular interactions of these cells, with the ultimate aim of suggesting a new potential therapeutic target for these lesions. We found that eosinophils were not involved in the fibrotic process and the variation of microscopic features in oral reactive lesions. Our results showed that peripheral giant-cell granulomas highly demonstrated histiocytic characteristics.

Comparison of injectable doxorubicin & its nanodrug complex chemotherapy for the treatment of 4-nitroquinoline-1-oxide induced oral squamous cell carcinoma in rats.

BACKGROUND & OBJECTIVES: Combination treatments of chemotherapy and nanoparticle drug delivery have shown significant promise in cancer treatment. The aim of the present study was to compare the efficacy of a nanodrug complex with its free form in the treatment of tongue squamous cell carcinoma induced by 4-nitroquinoline-1-oxide in rats. METHODS: In this study, 75 male Sprague-Dawley rats were divided into five groups. Oral squamous cell carcinoma (OSCC) was induced by using 4- nitroquinoline-1-oxide (4NQO) as a carcinogen. Newly formulated doxorubicin (DOX)-methotrexate (MTX)-loaded nanoparticles, and free DOX-MTX were administrated intravenously to rats. During the study, the animals were weighed once a week. At the end of the treatment, rats' tongues were evaluated histopathologically. RESULTS: There was significant difference between the mean weight of rats in groups A and B (P=0.001) and also groups A and K (P<0.001). No significant association was found between the mortality rate of groups. The difference between the severity of dysplasia of treated and untreated groups was significant (P<0.001). INTERPRETATION & CONCLUSIONS: Our study showed that DOX-MTX nanoparticle complex was more effective than free DOX-MTX in chemotherapy treatment of oral squamous cell carcinoma in rat models. Further investigations are necessary to clarify the advantages and disadvantages of the nanoparticle complex and its potential therapeutic application for different types of cancer.

Effects of systemic administration of HESA-A on the expression of cyclin D1 and EGFR and E-cadherin in the induced tongue dysplasia in rats.

Background. HESA-A has herbal and marine bases, containing minerals and rare elements such as Zr, Cr, Ga, Mn, Mg, Ca, Sr, Cu, Ti, etc. Its mechanism of action includes antioxidant, antiinflammatory and adjustment of the immune system. The aim of this study was to evaluate the effects of HESA-A systemic drug on expression of cyclin D1, EGFR and E-cadherin in induced tongue dysplasia in rats. Methods. In this experimental study, the effects of the systemic drug HESA-A on the expression of cyclin D1, EGFR, and E-cadherin molecular markers were examined in induced tongue dysplasia in rats. Results. The incidence rate of cyclin D1 in groups receiving HESA-A was lower than the group that did not receive the drug (77.78% in the 0‒5% range versus 77.78% in the 5‒50% range). In the case of expression of E-cadherin in group D, which did not receive HESA-A, a decrease was observed in the expression of this cell adhesion marker as compared to the other two groups. The incidence of E-cadherin was dependent on HESA-A dose, while with 500 mg/kg it was higher than other groups (>75% in 55.55% versus >75% in 11.11%). Concerning the incidence of EGFR in all the three groups most cases were grade 0. Conclusion. The results of the present research indicated that considering changes in the expression of cyclin D1 and E-cadherin markers in groups treated with HESA-A, HESA-A® has preventive effects on development of cancer in dysplastic lesions through regulation of expression of these molecules.

Immunohistochemical expression of Src protein in peripheral and central giant cell granulomas of the jaws.

AIM AND OBJECTIVE: The aim of this study was to investigate the expression of Src protein (an osteoclastic factor) in peripheral and central giant cell granulomas (PGCG and CGCGs) of the jaws and the relationship between the expression of this protein and the clinical behavior of these two lesions. MATERIALS AND METHODS: Thirty cases of PGCG and 30 cases of CGCG were immunohistochemically stained with Src. A staining-intensity-distribution (SID) score (proportion of stained cells × staining intensity) was used to evaluate immunoreactivity of the protein. Data were analyzed using statistical package for social sciences (SPSS) 17.0. RESULTS: There were no significant differences in the Src expression and the SID score between PGCG and CGCG. Furthermore, Spearman's rank correlation coefficient showed that there was a significant correlation between Src expression and SID score within both PGCG and CGCG (P < 0.001; r = 0.87 and 0.75, respectively). CONCLUSION: The findings of this study suggest that the multinucleated giant cells share some similarities with osteoclasts and Src protein can be used as a new therapeutic target to inhibit osteoclastic activity. In addition, differences in immunoreactivity of this osteoclastic protein do not reflect different clinical behaviors of PGCG and CGCG.